Epithelial cells of die adult mammalian colon have been particularly difficult to culture. The availability of human colonic epithelial cultures would provide new approaches for the study of normal colonic cell function as well as intestinal disease. The investigation of Inflammatory Bowel Disease (Crohn's disease and ulcerative colitis) is only one area of research that would reap immediate benefits from the availability of such cultures. To date very little is known of the role played by the colonic epithelial cell in this family of diseases. There exists the possibility that the colonic epithelial cell is an active participant in the disease process since it has recently been demonstrated that this cell can acquire antigen presenting function under select circumstances. However, definitive experiments to probe the nature of lymphocyte-epithelial interactions under a variety of conditions are not possible until pure colonic epithelial cultures can be generated reproducibly and quickly. We have recently developed a culture system for adult rabbit and human colonic epithelia. These cultures will be used as model systems to develop culture methodology for the growth of human colonic epithelial cells. The approach will involve a systematic study of the effects of growth factors, extracellular matrices, inflammatory mediators on the in vitro growth and differentiation of colonic epithelia. In the course of the investigations it will be necessary to develop some colon specific probes to assess the differentiative capability of the cultures. Additionally, since it is recognized that colonic epithelia differ in various respects among different regions of the colon, proximal and distal rabbit colon cultures will be used to investigate the nature of this difference. Initially, these studies will examine growth responses to various factors and hormones. The data generated will lead to studies of the underlying molecular mechanism(s) regulating colonic segmental diversity.